7.0 Project Summary/Abstract Links between chronic disease and cancer risk have been emphasized at various levels, including the World Health Organization. In terms of susceptibility to cancer, individuals with systemic lupus (SLE) have been shown to have distinct cancer risk profiles. Compared to the general population, current data indicate a slight increase in cancer in SLE overall. Within these data, the most evident increased risk is of hematologic cancers, specifically non-Hodgkin lymphoma. In contrast, certain cancers, such as breast, endometrial, and ovarian cancers, may have a decreased risk in persons with SLE, according to recent data. Though, in the past 10 years, a lot has been learnt regarding cancer risk in SLE, much remains unknown. Potentially, both SLE activity itself, and some of the drugs used to treat it, might serve as risk factors for certain malignancies; however, potentially some agents could protect against other cancer types, e.g. breast cancer. Though evidence points to a link between SLE and a decreased risk of breast cancer, the etiology behind this association is unknown. This provides further motivation for more research in this complex field. The primary objectives of our application are: 1. To describe breast cancer cases from an large SLE cohort, with respect to demographics and histology. 2. To assess the importance of drug exposures in persons SLE, regarding breast cancer risk. Here we will estimate the effects of selected medication exposures, adjusting for demographics, reproductive history, smoking and other clinical factors (SLE duration and activity). As secondary objectives, we will determine 1 and 5 year survival rates in the SLE patients who developed breast cancer. Our analyses will be based on data obtained from our multi-site international cohort study of over 16,000 SLE patients. Cancer cases have been ascertained via tumor registry linkage. Relevance: By studying a population like women with SLE, who have such a striking decreased risk of breast cancer, we may learn lessons that can be used to better understand interactions between various risk factors for cancer in the general population. Our project acknowledges that cancer etiology is multi-factorial, and will provide a better understanding of how different factor modify and interact in cancer pathogenesis. Our application answers to several high-priority areas in cancer epidemiology research identified by NIH and the National Cancer Institute, including identification of risk/susceptibility factors, and clinical and translational epidemiolog.